Imidazonaphthyridines

ABSTRACT

Tetrahydropyrido compounds of formula (I)                    
     in which the substituents have the meanings mentioned in the description, are suitable for the prevention or treatment of gastrointestinal diseases.

This application is a 371 of PCT/EP99/08227 filed Oct. 29, 1999, now WO00/28217 May 11, 2000.

FIELD OF APPLICATION OF THE INVENTION

The invention relates to novel compounds which are used in thepharmaceuticals industry as active compounds for preparing medicaments.

KNOWN TECHNICAL BACKGROUND

U.S. Pat. No. 4,468,400 describes tricyclic imidazo[1,2-a]pyridineshaving different ring systems fused to the imidazopyridine skeleton,which compounds are said to be suitable for treating peptic ulcerdisorders. The International Patent Application WO98/42707 disclosestetrahydroimidazonaphthyridines having a very particular substitutionpattern, which compounds are likewise said to be suitable for treatinggastrointestinal disorders.

DESCRIPTION OF THE INVENTION

The invention provides compounds of the formula I

in which

R1 is 1-4C-alkyl,

R2 is 1-4C-alkyl or hydroxy-1-4C-alkyl,

R3 is hydrogen or halogen,

one of the substituents R4a and R4b is hydrogen and the other ishydrogen, hydroxyl, 1-4C-alkoxy, 1-4C-alkoxy-1-4C-alkoxy,1-4C-alkylcarbonyloxy or the radical R4′, or R4a and R4b together are O(oxygen),

where

R4′ is

—O—(CH₂)_(m)S(O)_(n)—R9,

—S(O),—(CH₂)_(m)—OH,

—S(O)_(n)—(CH₂)_(m)—O—R9,

—S(O)_(n)—(CH₂)_(m)—S(O)_(p)—R9,

—O-alk1-S(O)_(n)—R9,

—S(O)_(n)—R9,

—S(O)_(n)-alk1-OH,

—S(O),-alk1-O—R9 or

—S(O),-alk1-S(O)_(p)—R9,

in which

R9 is 1-7C-alkyl, halo-1-4C-alkyl, hydroxy-1-4C-alkyl,1-4C-alkoxy-1-4C-alkyl, carboxy-1-4C-alkyl,1-4C-alkoxycarbonyl-1-4C-alkyl or di-1-4C-alkylamino-1-4C-alkyl, Ar orAr-1-4C-alkyl, where Ar is phenyl or substituted phenyl having one, twoor three identical or different substituents selected from the groupconsisting of 1-4C-alkyl, 1-4C-alkoxy, 1-4C-alkylcarbonyl,1-4C-alkoxycarbonyl, halogen, trifluoromethyl, difluoromethoxy,trifluoromethoxy, amino, 1-4C-alkoxycarbonylamino,1-4C-alkoxy-1-4C-alkoxycarbonylamino and nitro,

alk1 is 1-4C-alkyl-, hydroxyl-, oxo-, carboxyl-, halogen-, amino-,1-4C-alkoxycarbonylamino- or phenyl-substituted 2-7C-alkylene or3-4C-alkenylene,

m is an integer from 2 to 7,

n is the number 0, 1 or 2 and

p is the number 0, 1 or 2,

one of the substituents R5a and R5b is hydrogen and the other ishydrogen, hydroxyl, 1-4C-alkoxy, 1-4C-alkoxy-1-4C-alkoxy,1-4C-alkylcarbonyloxy or the radical R5′, or R5a and R5b together are O(oxygen),

where

R5′ is

—O—(CH₂)_(q)—S(O)_(r)—R10,

—S(O)_(r)(CH₂)_(q)—OH,

—S(O)_(r)(CH₂)_(q)—O—R10,

—S(O)_(r)(CH₂)_(q)—S(O)_(t)—R10,

—O-alk2-S(O)_(r)—R10,

—S(O)_(r)—R10,

—S(O)_(r)-alk2-OH,

—S(O)_(r)-alk2-O—R10 or

—S(O)_(r)-alk2-S(O)_(t)—R10,

in which

R10 is 1-7C-alkyl, halo-1-4C-alkyl, hydroxy-1-4C-alkyl,1-4C-alkoxy-1-4C-alkyl, carboxy-1-4C-alkyl,1-4C-alkoxycarbonyl-1-4C-alkyl or di-1-4C-alkylamino-1-4C-alkyl, Ar orAr-1-4C-alkyl, where Ar is phenyl or substituted phenyl having one, twoor three identical or different substituents selected from the groupconsisting of 1-4C-alkyl, 1-4C-alkoxy, 1-4C-alkylcarbonyl,1-4C-alkoxycarbonyl, halogen, trifluoromethyl, difluoromethoxy,trifluoromethoxy, amino, 1-4C-alkoxycarbonylamino,1-4C-alkoxy-1-4C-alkoxycarbonylamino and nitro,

alk2 is 1-4C-alkyl-, hydroxyl-, oxo-, carboxyl-, halogen-, amino-,1-4C-alkoxycarbonylamino- or phenyl-substituted 2-7C-alkylene or3-4C-alkenylene,

q is an integer from 2 to 7,

r is the number 0, 1 or 2 and

t is the number 0, 1 or 2,

R6 is hydrogen, halogen, 1-4C-alkyl, 1-4C-alkoxy,1-4C-alkoxycarbonylamino, 1-4C-alkoxy-1-4C-alkoxycarbonylamino ortrifluoromethyl,

R7 is hydrogen, halogen, 1-4C-alkyl or 1-4C-alkoxy and

R8 is hydrogen or 1-4C-alkyl,

and their salts,

where one of the substituents R4a and R4b has to be R4′and/or one of thesubstituents R5a and R5b has to be R5′.

1-4C-Alkyl represents straight-chain or branched alkyl radicals having 1to 4 carbon atoms. Examples which may be mentioned are the butyl,isobutyl, sec-butyl, tert-butyl, propyl, isopropyl, ethyl and methylradicals.

Hydroxy-1-4C-alkyl represents the abovementioned 1-4C-alkyl radicals,substituted by a hydroxyl group. Examples which may be mentioned are thehydroxymethyl, the 2-hydroxyethyl and the 3-hydroxypropyl radicals.

For the purpose of the invention, halogen is bromine, chlorine andfluorine.

1-4C-Alkoxy represents radicals which, in addition to the oxygen atom,contain a straight-chain or branched alkyl radical having 1 to 4 carbonatoms. Examples which may be mentioned are the butoxy, isobutoxy,sec-butoxy, tert-butoxy, propoxy, isopropoxy and preferably the ethoxyand methoxy radicals.

1-4C-Alkoxy-1-4C-alkoxy represents one of the abovementioned 1-4C-alkoxyradicals which is substituted by a further 1-4C-alkoxy radical. Exampleswhich may be mentioned are the radicals2-(methoxy)ethoxy(CH₃—O—CH₂—CH₂—O—) and2-(ethoxy)-ethoxy(CH₂—CH₂—O—CH₂—CH₂—O—).

1-4C-Alkylcarbonyl represents a radical which, in addition to thecarbonyl group, contains one of the abovementioned 1-4C-alkyl radicals.An example which may be mentioned is the acetyl radical.

1—4C-Alkylcarbonyloxy represents a carbonyloxy group to which isattached one of the abovementioned 1-4C-alkyl radicals. An example whichmay be mentioned is the acetoxy radical (CH₃CO—O—).

1-7C-Alkyl represents straight-chain or branched alkyl radicals having 1to 7 carbon atoms. Examples which may be mentioned are the heptyl,isoheptyl (5-methylhexyl), hexyl, isohexyl(4-methylpentyl),neohexyl(3,3-dimethylbutyl), pentyl, isopentyl(3-methylbutyl),neopentyl(2,2-dimethylpropyl), butyl, iso-butyl, sec-butyl, tert-butyl,propyl, isopropyl, ethyl and methyl radicals.

Halo-1-4C-alkyl represents one of the abovementioned 1-4C-alkyl radicalswhich is substituted by one of the abovementioned halogen atoms. Anexample which may be mentioned is the 3-chloropropyl radical.

1-4C-Alkoxy-1-4C-alkyl represents one of the above-mentioned 1-4C-alkylradicals which is substituted by one of the abovementioned 1-4C-alkoxyradicals. Examples which may be mentioned are the methoxymethyl, themethoxyethyl and the butoxyethyl radicals.

Carboxy-1-4alkyl represents, for example, the carboxy-methyl (—CH₂COOH)or the carboxyethyl (—CH₂CH₂COOH) radicals.

1-4C-Alkoxycarbonyl represents a carbonyl group to which is attached oneof the abovementioned 1-4C-alkoxy radicals. Examples which may bementioned are the methoxycarbonyl (CH₃O—C(O)—) and the ethoxycarbonyl(CH₃CH₂O—C(O)—) radicals.

1-4C-Alkoxycarbonyl-1-4C-alkyl represents one of the abovementioned1-4C-alkyl radicals which is substituted by one of the abovementioned1-4C-alkoxycarbonyl radicals. An example which may be mentioned is theethoxycarbonylmethyl radical (CH₃CH₂OC(O)CH₂—).

Di-1-4C-alkylamino represents an amino radical which is substituted bytwo of the abovementioned 1-4C-alkyl radicals, which may be identical ordifferent. Examples which may be mentioned are the dimethylamino, thediethylamino and the diisopropylamino radicals.

Di-1-4C-alkylamino-1-4C-alkyl represents one of the abovementioned1-4C-alkyl radicals which is substituted by one of the abovementioneddi-1-4C-alkylamino radicals. Examples which may be mentioned are thedimethylaminomethyl, the dimethylaminoethyl and the diethylaminoethylradicals.

Ar-1-4C-alkyl represents one of the abovementioned 1-4C-alkyl radicalswhich is substituted by Ar, where Ar is as defined above. Examples whichmay be mentioned are the phenethyl and the benzyl radicals.

1-4C-Alkoxycarbonylamino represents an amino radical which issubstituted by one of the abovementioned 1-4C-alkoxycarbonyl radicals.Examples which may be mentioned are the ethoxycarbonylamino and themethoxycarbonylamino radicals.

1-4C-Alkoxy-1-4C-alkoxycarbonyl represents a carbonyl group to which isattached one of the abovementioned 1-4C-alkoxy-1-4C-alkoxy radicals.Examples which may be mentioned are the 2-(methoxy)ethoxycarbonyl(CH₃—O—CH₂CH₂—CO—) and the 2-(ethoxy)ethoxycarbonyl(CH₃CH₂—O—CH₂CH₂—O—CO—) radicals.

1-4C-Alkoxy-1-4C-alkoxycarbonylamino represents an amino radical whichis substituted by one of the abovementioned1-4C-alkoxy-1-4C-alkoxycarbonyl radicals. Examples which may bementioned are the 2-(methoxy)-ethoxycarbonylamino and the2-(ethoxy)ethoxycarbonylamino radicals.

1-7C-Alkylene represents straight-chain or branched 1-7C-alkeneradicals, for example the methylene (—CH₂—), ethylene (—CH₂—CH₂—),tetramethylene (—CH₂—CH₂—CH₂—), tetramethylene (—CH₂—CH₂—CH₂—CH₂—),1,2-dimethylethylene [—CH(CH₃)—CH(CH₃)—], 1,1-dimethylethylene[—C(CH₃)₂—CH₂—], 2,2-dimethylethylene [—CH₂—C(CH₃)₂—],1,1-isopropylidene [—C(CH₃)₂—], 1-methylethylene [—CH(CH₃)—CH₂—],pentamethylene [—CH₂—CH₂—CH₂—CH₂—CH₂), hexamethylene(—CH₂—CH₂—CH₂—CH₂—CH₂—CH₂—) and the heptamethylene(—CH₂—CH₂—CH₂—CH₂—CH₂—CH₂—CH₂—) radicals.

3-4C-Alkenylene represents straight-chain 3-4C-alkenylene radicals, forexample the 1-propenylene, the 2-propenylene, the 2-butenylene and the3-butenylene radicals.

Suitable salts of compounds of the formula I are—depending on thesubstitution—in particular all acid addition salts. Particular mentionmay be made of the pharmacologically acceptable salts of the inorganicand organic acids customarily used in pharmacy. Those suitable arewater-soluble and water-insoluble acid addition salts with acids suchas, for example, hydrochloric acid, hydrobromic acid, phosphoric acid,nitric acid, sulfuric acid, acetic acid, citric acid, D-gluconic acid,benzoic acid, 2-(4-hydroxybenzoyl)benzoic acid, butyric acid,sulfosalicylic acid, maleic acid, lauric acid, malic acid, fumaric acid,succinic acid, oxalic acid, tartaric acid, embonic acid, stearic acid,toluenesulfonic acid, methanesulfonic acid or 3-hydroxy-2-naphthoicacid, where the acids are employed in the salt preparation in anequimolar ratio or a ratio differing therefrom, depending on whether theacid is a mono- or polybasic acid and on which salt is desired.

Pharmacologically unacceptable salts, which can be initially obtained,for example, as process products in the preparation of the compoundsaccording to the invention on an industrial scale, are converted intopharmacologically acceptable salts by processes known to the personskilled in the art.

It is known to the person skilled in the art that the compoundsaccording to the invention and their salts can, for example when theyare isolated in crystalline form, comprise varying amounts of solvents.The invention therefore also embraces all solvates and, in particular,all hydrates of the compounds of the formula I, and all solvates and, inparticular, all hydrates of the salts of the compounds of the formula I.

The compounds of the formula I have at least three chiral centers. Theinvention provides all eight feasible stereoisomers in any mixing ratio,including the pure enantiomers which are the preferred subject matter ofthe invention.

An exemplary preferred radical R1 is the methyl radical.

Exemplary preferred radicals R2 are the methyl and the hydroxymethylradicals.

In the context of the present invention, R3 is preferably hydrogen.

Exemplary radicals R9 or R10 which may be mentioned are: methyl, ethyl,propyl, isopropyl, butyl, isobutyl, pentyl, difluoromethyl,2,2,2-trifluoroethyl, 2-hydroxy-ethyl, 3-hydroxypropyl, methoxymethyl,methoxyethyl, ethoxymethyl, ethoxyethyl, carboxymethyl, carboxyethyl,carboxypropyl, methoxycarbonylmethyl, dimethylaminoethyl,diethylaminoethyl, phenyl, benzyl, 4-chlorophenyl, 4-aminophenyl,4-chlorobenzy], 4-difluoromethoxyphenyl, 4-trifluoromethoxyphenyl,4-methylbenzyl, 3-methylbenzyl, 2,4-diaminophenyl,2-methyl-4-tert-butylphenyl, 2-nitro-4-acetylphenyl, 4-fluorobenzyl,4-nitrophenyl, 3-nitrophenyl, 3-aminophenyl,2-methoxycarbonylamino-6-methylphenyl,2-methoxyethoxycarbonylamino-6-methylphenyl,2-methoxycarbonylamino-6-methylbenzyl and2-methoxyethoxycarbonylamino-6-methylbenzyl.

Exemplary alkylene and alkenylene groups alk1 and alk2, respectively,which may be mentioned are: 1-methylethylene, 2-methylethylene,1-phenylethylene, 2-phenylethylene, 1-propylpropylene,3-propylpropylene, 2-aminopropylene,2-tert-butyloxycarbonylaminopropylene, 2-hydroxypropylene,2-oxopropylene, 2-carboxypropylene, 1-acetyl-1,2-dimethylethylene,2-acetyl-1,2-dimethylethylene, 1,1-dimethyl-2-oxoethylene,1-oxo-2,2-dimethylethylene, 1,3-dioxobutylene, 2,4-dioxobutylene,1,2-dioxopropylene, 2,3-dioxopropylene, prop-1-enylene, prop-2-enylene,but-1-enylene, but-2-enylene, but-3-enylene, but-4-enylene,buta-1,3-dienylene, buta-2,4-dienylene, 1-oxo-but-2-enylene,4-oxo-but-2-enylene, 1-oxo-2,2-difluoroethylene,2-oxo-1,1-difluoroethylene, 1-oxopropylene, 3-oxopropylene,1-carboxyethylene and 2-carboxyethylene.

Compounds which may be mentioned are those of the formula I in which

R1 is 1-4C-alkyl,

R2 is 1-4C-alkyl or hydroxy-1-4C-alkyl,

R3 is hydrogen,

one of the substituents R4a and R4b is hydrogen and the other ishydrogen, hydroxyl, 1-4C-alkoxy, 1-4C-alkoxy-1-4C-alkoxy or the radicalR4′,

where

R4′ is

—O—(CH₂)_(m)—S(O)_(n)—R9,

—S(O)_(n)—(CH₂)_(m)—OH,

—S(O)_(n)—(CH₂)_(m)—O—R9,

—S(O)_(n)—(CH₂)_(m)—S(O)_(p)—R9 or

—S(O)_(n)—R9,

in which

R9 is 1-7C-alkyl, halo-1-4C-alkyl, hydroxy-1-4C-alkyl or1-4C-alkoxy-1-4C-alkyl,

m is an integer from 2 to 7,

n is the number 0, 1 or 2 and

p is the number 0, 1 or 2,

one of the substituents R5a and R5b is hydrogen and the other ishydrogen, hydroxyl, 1-4C-alkoxy, 1-4C-alkoxy-1-4C-alkoxy or the radicalR5′,

where

R5′ is

—O—(CH₂)_(q)—S(O)_(r)R10,

—S(O)_(r)—(CH₂)_(q)—OH,

—S(O)_(r)—(CH₂)_(q)—O—R10,

—S(O)_(r)—(CH₂)_(q)—S(O)_(t)—R10, or

—S(O)_(r)—R10,

in which

R10 is 1-7C-alkyl, halo-1-4C-alkyl, hydroxy-1-4C-alkyl or1-4C-alkoxy-1-4C-alkyl,

q is an integer from 2 to 7,

r is the number 0, 1 or 2 and

t is the number 0, 1 or 2,

R6 is hydrogen, halogen or trifluoromethyl,

R7 is hydrogen or halogen and

R8 is hydrogen,

and their salts,

where one of the substituents R4a and R4b has to be R4′ and/or one ofthe substituents R5a and R5b has to be R5′.

Compounds according to the invention which are to be emphasized arethose of the formula I*

in which

R1 is 1-4C-alkyl,

R2 is 1-4C-alkyl or hydroxy-1-4C-alkyl,

R3 is hydrogen,

one of the substituents R4a and R4b is hydrogen and the other ishydrogen, hydroxyl, 1-4C-alkoxy, 1-4C-alkoxy-1-4C-alkoxy or the radicalR4′,

where

R4′ is

—O—(CH₂)_(m)—S(O)_(n)—R9,

—S(O)_(n)—(CH₂)_(m)—OH,

—S(O)_(n)—(CH₂)_(m)—O—R9,

—S(O)_(n)—(CH₂)_(m)—S(O)_(p)—R9 or

—S(O)_(n)—R9,

in which

R9 is 1-7C-alkyl, halo-1-4C-alkyl, hydroxy-1-4C-alkyl or1-4C-alkoxy-1-4C-alkyl,

m is an integer from 2 to 7,

n is the number 0, 1 or 2 and

p is the number 0, 1 or 2,

one of the substituents R5a and R5b is hydrogen and the other ishydrogen, hydroxyl, 1-4C-alkoxy, 1-4C-alkoxy-1-4C-alkoxy or the radicalR5′,

where

R5′ is

—O—(CH₂)_(q)—S(O)_(r)—R10,

—S(O)_(r)—(CH₂)_(q)—OH,

—S(O)_(r)—(CH₂)_(q)—O—R10,

—S(O)_(r)—(CH₂)_(q)—S(O)_(t)R10 or

—S(O)_(r)—R10,

in which

R10 is 1-7C-alkyl, halo-1-4C-alkyl, hydroxy-1-4C-alkyl or1-4C-alkoxy-1-4C-alkyl,

q is an integer from 2 to 7,

r is the number 0, 1 or 2 and

t is the number 0, 1 or 2,

R6 is hydrogen, halogen or trifluoromethyl,

R7 is hydrogen or halogen and

R8 is hydrogen,

and their salts,

where one of the substituents R4a and R4b has to be R4′ and/or one ofthe substituents R5a and R5b has to be R5′.

One embodiment (embodiment a) of the compounds of the formula I* to beemphasized are those in which

one of the substituents R4a and R4b is hydrogen and the other is theradical R4′ and one of the substituents R5a and R5b is hydrogen and theother is hydroxyl.

A further embodiment (embodiment b) of the compounds of the formula I*to be emphasized are those in which

one of the substituents R4a and R4b is hydrogen and the other is theradical R4′ and one of the substituents R5a and R5b is hydrogen and theother is 1-4C-alkoxy or 1-4C-alkoxy-1-4C-alkoxy.

A further embodiment (embodiment c) of the compounds of the formula I*to be emphasized are those in which

one of the substituents R4a and R4b is hydrogen and the other is theradical R4′ and one of the substituents R5a and R5b is hydrogen and theother is the radical R5′.

A further embodiment (embodiment d) of the compounds of the formula I*to be emphasized are those in which

one of the substituents R4a and R4b is hydrogen and the other is1-4C-alkoxy or 1-4C-alkoxy-1-4C-alkoxy and one of the substituents R5aand R5b is hydrogen and the other is the radical R5′.

Compounds I* of the embodiments a, b, c and d which are to be emphasizedparticularly are those in which

R1 is 1-4C-alkyl,

R2 is 1-4C-alkyl,

R3 is hydrogen,

R4′ is

—O—(CH₂)_(m)—S(O)_(n)—R9,

—S(O)_(n)—R9,

—S(O)_(n)—(CH₂)_(m)—OH or

—S(O)_(n)—(CH₂)_(m)—O—R9,

in which R9 is 1-4C-alkyl,

R5′ is

—O—(CH₂)_(q)—S(O)_(r)R10,

—S(O)_(r)—R10,

—S(O)_(r)—(CH₂)_(q)—OH or

—S(O)_(r)—(CH₂)_(q)—O—R10,

in which R10 is 1-4C-alkyl,

R6 is hydrogen,

R7 is hydrogen and

R8 is hydrogen,

and their salts.

Preferred compounds I* of the embodiment a are those in which

R1 is 1-4C-alkyl,

R2 is 1-4C-alkyl,

R3 is hydrogen,

one of the substituents R4a and R4b is hydrogen and the other is R4′,

where

R4′ is

—O—(CH₂)_(m)—S(O)_(n)—R9,

—S(O)_(n)—R9,

—S(O)_(n)—(CH₂)_(m)—OH or

—S(O)_(n)—(CH₂)_(m)—O—R9,

in which R9 is 1-4C-alkyl,

m is the number 2 or 3 and

n is the number 0, 1 or 2,

one of the substituents R5a and R5b is hydrogen and the other ishydroxyl,

R6 is hydrogen,

R7 is hydrogen and

R8 is hydrogen,

and their salts.

Preferred compounds I* of the embodiment b are those in which

R1 is 1-4C-alkyl,

R2 is 1-4C-alkyl,

R3 is hydrogen,

one of the substituents R4a and R4b is hydrogen and the other is R4′,

where

R4′ is

—O—(CH₂)_(m)—S(O)_(n)—R9,

—S(O)_(n)—R9,

—S(O)_(n)—(CH₂)_(m)—OH or

—S(O)_(n)—(CH₂)_(m)—O—R9,

in which R9 is 1-4C-alkyl,

m is the number 2 or 3 and

n is the number 0,1 or 2,

one of the substituents R5a and R5b is hydrogen and the other is1-4C-alkoxy or 1-4C-alkoxy-1-4C-alkoxy,

R6 is hydrogen,

R7 is hydrogen and

R8 is hydrogen,

and their salts.

Preferred compounds I* of the embodiment c are those in which

R1 is 1-4C-alkyl,

R2 is 1-4C-alkyl,

R3 is hydrogen,

one of the substituents R4a and R4b is hydrogen and the other is R4′,

where

R4′ is

—O—(CH₂)_(m)—S(O)_(n)—R9,

—S(O)_(n)—R9,

—S(O)_(n)—(CH₂)_(m)—OH or

—S(O)_(n)—(CH₂)_(m)—O—R9,

in which R9 is 1-4C-alkyl,

m is the number 2 or 3 and

n is the number 0, 1 or 2,

one of the substituents R5a and R5b is hydrogen and the other is R5′,

where

R5′ is

—O—(CH₂)_(q)—S(O)_(r)—R10,

—S(O)_(r)—R10,

—S(O)_(r)—(CH₂)_(q)—OH or

—S(O)_(r)—(CH₂)_(q)—O—R10,

in which R10 is 1-4C-alkyl,

q is the number 2 or 3 and

r is the number 0,1 or 2,

R6 is hydrogen,

R7 is hydrogen and

R8 is hydrogen,

and their salts.

Preferred compounds I* of the embodiment d are those in which

R1 is 1-4C-alkyl,

R2 is 1-4C-alkyl,

R3 is hydrogen,

one of the substituents R4a and R4b is hydrogen and the other is1-4C-alkoxy or 1-4C-alkoxy-1-4C-alkoxy

one of the substituents R5a and R5b is hydrogen and the other is R5′,

where

R5′ is

—O—(CH₂)_(q)—S(O)_(n)—R10,

—S(O)_(r)—R10,

—S(O)_(r)—(CH₂)_(q)—OH or

—S(O)_(r)—(CH₂)_(q)—O—R10,

in which R10 is 1-4C-alkyl,

q is the number 2 or 3 and

r is the number 0, 1 or 2,

R6 is hydrogen

R7 is hydrogen and

R8 is hydrogen,

Selected preferred compounds I* are those of the embodiments a, b, c andd in which R5b is hydrogen.

Selected particularly preferred compounds I* are those of theembodiments a, b, c and d in which R5b is hydrogen and R4a is hydrogen.

The following preferred compounds according to the invention selected byway of example may be mentioned specifically using formula I* below withthe substituent definitions for R4a, R4b and R5a of Table 1 (Tab. 1)below:

TABLE 1

R4a R4b R5a H —OCH₂CH₂SCH₃ —OH H —OCH₂CH₂SOCH₃ —OH H —OCH₂CH₂SO₂CH₃ —OHH —SCH₂CH₂OCH₃ —OH H —SOCH₂CH₂OCH₃ —OH H —SO₂CH₂CH₂OCH₃ —OH H —SCH₂CH₂OH—OH H —SCH₃ —OH H —SOCH₃ —OH H —SO₂CH₃ —OH H —SCH₂CH₃ —OH H —SOCH₂CH₃—OH H —SO₂CH₂CH₃ —OH H —SCH₂CH₂CH₃ —OH H —SOCH₂CH₂CH₃ —OH H—SO₂CH₂CH₂CH₃ —OH H —SCH(CH₃)₂ —OH H —SOCH(CH₃)₂ —OH H —SO₂CH(CH₃)₂ —OHH —SCH₂COOCH₂CH₃ —OH H —SOCH₂COOCH₂CH₃ —OH H —SO₂CH₂COOCH₂CH₃ —OH—OCH₂CH₂SCH₃ H —OH —OCH₂CH₂SOCH₃ H —OH —OCH₂CH₂SO₂CH₃ H —OH —SCH₂CH₂OCH₃H —OH —SOCH₂CH₂OCH₃ H —OH —SO₂CH₂CH₂OCH₃ H —OH —SCH₂CH₂OH H —OH —SCH₃ H—OH —SOCH₃ H —OH —SO₂CH₃ H —OH —SCH₂CH₃ H —OH —SOCH₂CH₃ H —OH —SO₂CH₂CH₃H —OH —SCH₂CH₂CH₃ H —OH —SOCH₃CH₂CH₃ H —OH —SO₂CH₂CH₂CH₃ H —OH—SCH(CH₃)₂ H —OH —SOCH(CH₃)₂ H —OH —SO₂CH(CH₃)₂ H —OH —SCH₂COOCH₂CH₃ H—OH —SOCH₂COOCH₂CH₃ H —OH —SO₂CH₂COOCH₂CH₃ H —OH H —OCH₂CH₂SCH₃ —OCH₃ H—OCH₂CH₂SOCH₃ —OCH₃ H —OCH₂CH₂SO₂CH₃ —OCH₃ H —SCH₂CH₂OCH₃ —OCH₃ H—SOCH₂CH₂OCH₃ —OCH₃ H —SO₂CH₂CH₂OCH₃ —OCH₃ H —SCH₂CH₂OH —OCH₃ H —SCH₃—OCH₃ H —SOCH₃ —OCH₃ H —SO₂CH₃ —OCH₃ H —SCH₂CH₃ —OCH₃ H —SOCH₂CH₃ —OCH₃H —SO₂CH₂CH₃ —OCH₃ H —SCH₂CH₂CH₃ —OCH₃ H —SOCH₂CH₂CH₃ —OCH₃ H—SO₂CH₂CH₂CH₃ —OCH₃ H —SCH(CH₃)₂ —OCH₃ H —SOCH(CH₃)₂ —OCH₃ H—SO₂CH(CH₃)₂ —OCH₃ H —SCH₂COOCH₂CH₃ —OCH₃ H —SOCH₂COOCH₂CH₃ —OCH₃ H—SO₂CH₂COOCH₂CH₃ —OCH₃ H —OCH₂CH₂SCH₃ —OCH₂CH₂OCH₃ H —OCH₂CH₂SOCH₃—OCH₂CH₂OCH₃ H —OCH₂CH₂SO₂CH₃ —OCH₂CH₂OCH₃ H —SCH₂CH₂OCH₃ —OCH₂CH₂OCH₃ H—SOCH₂CH₂OCH₃ —OCH₂CH₂OCH₃ H —SO₂CH₂CH₂OCH₃ —OCH₂CH₂OCH₃ H —SCH₂CH₂OH—OCH₂CH₂OCH₃ H —SCH₃ —OCH₂CH₂OCH₃ H —SOCH₃ —OCH₂CH₂OCH₃ H —SO₂CH₃—OCH₂CH₂OCH₃ H —SCH₂CH₃ —OCH₂CH₂OCH₃ H —SOCH₂CH₃ —OCH₂CH₂OCH₃ H—SO₂CH₂CH₃ —OCH₂CH₂OCH₃ H —SCH₂CH₂CH₃ —OCH₂CH₂OCH₃ H —SOCH₂CH₂CH₃—OCH₂CH₂OCH₃ H —SO₂CH₂CH₂CH₃ —OCH₂CH₂OCH₃ H —SCH(CH₃)₂ —OCH₂CH₂OCH₃ H—SOCH(CH₃)₂ —OCH₂CH₂OCH₃ H —SO₂CH(CH₃)₂ —OCH₂CH₂OCH₃ H —SCH₂COOCH₂CH₃—OCH₂CH₂OCH₃ H —SOCH₂COOCH₂CH₃ —OCH₂CH₂OCH₃ H —SO₂CH₂COOCH₂CH₃—OCH₂CH₂OCH₃ —OCH₂CH₂SCH₃ H —OCH₃ —OCH₂CH₂SOCH₃ H —OCH₃ —OCH₂CH₂SO₂CH₃ H—OCH₃ —SCH₂CH₂OCH₃ H —OCH₃ —SOCH₂CH₂OCH₃ H —OCH₃ —SO₂CH₂CH₂OCH₃ H —OCH₃—SCH₂CH₂OH H —OCH₃ —SCH₃ H —OCH₃ —SOCH₃ H —OCH₃ —SO₂CH₃ H —OCH₃ —SCH₂CH₃H —OCH₃ —SOCH₂CH₃ H —OCH₃ —SO₂CH₂CH₃ H —OCH₃ —SCH₂CH₂CH₃ H —OCH₃—SO₂CH₂CH₂CH₃ H —OCH₃ —SO₂CH₂CH₂CH₃ H —OCH₃ —SCH(CH₃)₂ H —OCH₃—SOCH(CH₃)₂ H —OCH₃ —SO₂CH(CH₃)₂ H —OCH₃ —SCH₂COOCH₂CH₃ H —OCH₃—SOCH₂COOCH₂CH₃ H —OCH₃ —SO₂CH₂COOCH₂CH₃ H —OCH₃ —OCH₂CH₂SCH₃ H—OCH₂CH₂OCH₃ —OCH₂CH₂SOCH₃ H —OCH₂CH₂OCH₃ —OCH₂CH₂SO₂CH₃ H —OCH₂CH₂OCH₃—SCH₂CH₂OCH₃ H —OCH₂CH₂OCH₃ —SOCH₂CH₂OCH₃ H —OCH₂CH₂OCH₃ —SO₂CH₂CH₂OCH₃H —OCH₂CH₂OCH₃ —SOCH₂CH₂CH H —OCH₂CH₂OCH₃ —SCH₃ H —OCH₂CH₂OCH₃ —SOCH₃ H—OCH₂CH₂OCH₃ —SO₂CH₃ H —OCH₂CH₂OCH₃ —SCH₂CH₃ H —OCH₂CH₂OCH₃ —SOCH₂CH₃ H—OCH₂CH₂OCH₃ —SO₂CH₂CH₃ H —OCH₂CH₂OCH₃ —SCH₂CH₂CH₃ H —OCH₂CH₂OCH₃—SOCH₂CH₂CH₃ H —OCH₂CH₂OCH₃ —SO₂CH₂CH₂CH₃ H —OCH₂CH₂OCH₃ —SCH(CH₃)₂ H—OCH₂CH₂OCH₃ —SO₂CH(CH₃)₂ H —OCH₂CH₂OCH₃ —SO₂CH(CH₃)₂ H —OCH₂CH₂OCH₃—SCH₂COOCH₂CH₃ H —OCH₂CH₂OCH₃ —SOCH₂COOCH₂CH₃ H —OCH₂CH₂OCH₃—SO₂CH₂COOCH₂CH₃ H —OCH₂CH₂OCH₃ —OCH₂CH₂SCH₃ H —OCH₂CH₂SCH₃—OCH₂CH₂SOCH₃ H —OCH₂CH₂SCH₃ —OCH₂CH₂SO₂CH₃ H —OCH₂CH₂SCH₃ —SCH₂CH₂OCH₃H —OCH₂CH₂SCH₃ —SOCH_(2CH) ₂OCH₃ H —OCH₂CH₂SCH₃ —SO₂CH₂CH₂OCH₃ H—OCH₂CH₂SCH₃ —SCH₂CH₂CH H —OCH₂CH₂SCH₃ —SCH₃ H —OCH₂CH₂SCH₃ —SOCH₃ H—OCH₂CH₂SCH₃ —SO₂CH₃ H —OCH₂CH₂SCH₃ —SCH₂CH₃ H —OCH₂CH₂SCH₃ —SOCH₂CH₃ H—OCH₂CH₂SCH₃ —SO₂CH₂CH₃ H —OCH₂CH₂SCH₃ —SCH₂CH₂CH₃ H —OCH₂CH₂SCH₃—SOCH₂CH₂CH₃ H —OCH₂CH₂SCH₃ —SO₂CH₂CH₂CH₃ H —OCH₂CH₂SCH₃ —SCH(CH₃)₂ H—OCH₂CH₂SCH₃ —SO₂CH(CH₃)₂ H —OCH₂CH₂SCH₃ —SO₂CH(CH₃)₂ H —OCH₂CH₂SCH₃—SCH₂COOCH₂CH₃ H —OCH₂CH₂SCH₃ —SOCH₂COOCH₂CH₃ H —OCH₂CH₂SCH₃—SO₂CH₂COOCH₂CH₃ H —OCH₂CH₂SCH₃ —OCH₂CH₂SCH₃ H —SCH₂CH₂OH —OCH₂CH₂SOCH₃H —SCH₂CH₂OH —OCH₂CH₂SO₂CH₃ H —SCH₂CH₂OH —SCH₂CH₂OCH₃ H —SCH₂CH₂OH—SOCH₂CH₂OCH₃ H —SCH₂CH₂OH —SO₂CH₂CH₂OCH₃ H —SCH₂CH₂OH —SCH₂CH₂OH H—SCH₂CH₂OH —SCH₃ H —SCH₂CH₂OH —SOCH₃ H —SCH₂CH₂OH —SO₂CH₃ H —SCH₂CH₂OH—SCH₂CH₃ H —SCH₂CH₂OH —SOCH₂CH₃ H —SCH₂CH₂OH —SO₂CH₂CH₃ H —SCH₂CH₂OH—SCH₂CH₂CH₃ H —SCH₂CH₂OH —SOCH₂CH₂CH₃ H —SCH₂CH₂OH —SO₂CH₂CH₂CH₃ H—SCH₂CH₂OH —SCH(CH₃)₂ H —SCH₂CH₂OH —SOCH(CH₃)₂ H —SCH₂CH₂OH —SO₂CH(CH₃)₂H —SCH₂CH₂OH —SCH₂COOCH₂CH₃ H —SCH₂CH₂OH —SOCH₂COOCH₂CH₃ H —SCH₂CH₂OH—SO₂CH₂COOCH₂CH₃ H —SCH₂CH₂OH —OCH₂CH₂SCH₃ H —SCH₃ —OCH₂CH₂SOCH₃ H —SCH₃—OCH₂CH₂SO₂CH₃ H —SCH₃ —SCH₂CH₂OCH₃ H —SCH₃ —SOCH₂CH₂OCH₃ H —SCH₃—SO₂CH₂CH₂OCH₃ H —SCH₃ —SCH₂CH₂OH H —SCH₃ —SCH₃ H —SCH₃ —SOCH₃ H —SCH₃—SO₂CH₃ H —SCH₃ —SCH₂CH₃ H —SCH₃ —SOCH₂CH₃ H —SCH₃ —SO₂CH₂CH₃ H —SCH₃—SCH₂CH₂CH₃ H —SCH₃ —SOCH₂CH₂CH₃ H —SCH₃ —SO₂CH₂CH₂CH₃ H —SCH₃—SCH(CH₃)₂ H —SCH₃ —SOCH(CH₃)₂ H —SCH₃ —SO₂CH(CH₃)₂ H —SCH₃—SCH₂COOCH₂CH₃ H —SCH₃ —SOCH₂COOCH₂CH₃ H —SCH₃ —SO₂CH₂COOCH₂CH₃ H —SCH₃—OCH₂CH₂SCH₃ H —SCH₂CH₂OCH₃ —OCH₂CH₂SOCH₃ H —SCH₂CH₂OCH₃ —OCH₂CH₂SO₂CH₃H —SCH₂CH₂OCH₃ —SCH₂CH₂OCH₃ H —SCH₂CH₂OCH₃ —SOCH₂CH₂OCH₃ H —SCH₂CH₂OCH₃—SO₂CH₂CH₂OCH₃ H —SCH₂CH₂OCH₃ —SCH₂CH₂OH H —SCH₂CH₂OCH₃ —SCH₃ H—SCH₂CH₂OCH₃ —SOCH₃ H —SCH₂CH₂OCH₃ —SO₂CH₃ H —SCH₂CH₂OCH₃ —SCH₂CH₃ H—SCH₂CH₂OCH₃ —SOCH₂CH₃ H —SCH₂CH₂OCH₃ —SO₂CH₂CH₃ H —SCH₂CH₂OCH₃—SCH₂CH₂CH₃ H —SCH₂CH₂OCH₃ —SOCH₂CH₂CH₃ H —SCH₂CH₂OCH₃ —SO₂CH₂CH₂CH₃ H—SCH₂CH₂OCH₃ —SCH(CH₃)₂ H —SCH₂CH₂OCH₃ —SOCH(CH₃)₂ H —SCH₂CH₂OCH₃—SO₂CH(CH₃)₂ H —SCH₂CH₂OCH₃ —SCH₂COOCH₂CH₃ H —SCH₂CH₂OCH₃—SOCH₂COOCH₂CH₃ H —SCH₂CH₂OCH₃ —SO₂CH₂COOCH₂CH₃ H —SCH₂CH₂OCH₃ H—OCH₂CH₂SCH₃ —OCH₂CH₂SCH₃ H —OCH₃CH₂SOCH₃ —OCH₂CH₂SCH₃ H —OCH₂CH₂SO₂CH₃—OCH₂CH₂SCH₃ H —SCH₂CH₂OCH₃ —OCH₂CH₂SCH₃ H —SOCH₂CH₂OCH₃ —OCH₂CH₂SCH₃ H—SO₂CH₂CH₂OCH₃ —OCH₂CH₂SCH₃ H —SCH₂CH₂OH —OCH₂CH₂SCH₃ H —SCH₃—OCH₃CH₂SCH₃ H —SOCH₃ —OCH₂CH₂SCH₃ H —SO₂CH₃ —OCH₂CH₂SCH₃ H —SCH₂CH₃—OCH₂CH₂SCH₃ H —SOCH₂CH₃ —OCH₂CH₂SCH₃ H —SO₂CH₂CH₃ —OCH₂CH₂SCH₃ H—SCH₂CH₂CH₃ —OCH₂CH₂SCH₃ H —SOCH₂CH₂CH₃ —OCH₂CH₂SCH₃ H —SO₃CH₂CH₂CH₃—OCH₂CH₂SCH₃ H —SCH(CH₃)₂ —OCH₂CH₂SCH₃ H —SOCH(CH₃)₂ —OCH₂CH₂SCH₃ H—SO₂CH(CH₃)₂ —OCH₂CH₂SCH₃ H —SCH₂COOCH₂CH₃ —OCH₂CH₂SCH₃ H—SOCH₂COOCH₂CH₃ —OCH₂CH₂SCH₃ H —SO₂CH₂COOCH₂CH₃ —OCH₂CH₂SCH₃ H—OCH₂CH₂SCH₃ —SCH₂CH₂OH H —OCH₂CH₂SOCH₃ —SCH₂CH₂OH H —OCH₂CH₂SO₂CH₃—SCH₂CH₂OH H —SCH₂CH₂OCH₃ —SCH₂CH₂OH H —SOCH₂CH₂OCH₃ —SCH₂CH₂OH H—SO₂CH₂CH₂OCH₃ —SCH₂CH₂OH H —SCH₂CH₂OH —SCH₂CH₂OH H —SCH₃ —SCH₂CH₂OH H—SOCH₃ —SCH₂CH₂OH H —SO₂CH₃ —SCH₂CH₂OH H —SCH₂CH₃ —SCH₂CH₂OH H —SOCH₂CH₃—SCH₂CH₂OH H —SO₂CH₂CH₃ —SCH₂CH₂OH H —SCH₂CH₂CH₃ —SCH₂CH₂OH H—SOCH₂CH₂CH₃ —SCH₂CH₂OH H —SO₂CH₂CH₂CH₃ —SCH₂CH₂OH H —SCH(CH₃)₂—SCH₂CH₂OH H —SOCH(CH₃)₂ —SCH₂CH₂OH H —SO₂CH(CH₃)₂ —SCH₂CH₂OH H—SCH₂COOCH₂CH₃ —SCH₂CH₂OH H —SOCH₂COOCH₂CH₃ —SCH₂CH₂OH H—SO₂CH₂COOCH₂CH₃ —SCH₂CH₂OH H —OCH₂CH₂SCH₃ —SCH₃ H —OCH₂CH₂SOCH₃ —SCH₃ H—OCH₂CH₂SO₂CH₃ —SCH₃ H —SCH₂CH₂OCH₃ —SCH₃ H —SOCH₂CH₂OCH₃ —SCH₃ H—SO₂CH₂CH₂OCH₃ —SCH₃ H —SCH₂CH₂OH —SCH₃ H —SCH₃ —SCH₃ H —SOCH₃ —SCH₃ H—SO₂CH₃ —SCH₃ H —SCH₂CH₃ —SCH₃ H —SOCH₂CH₃ —SCH₃ H —SO₂CH₂CH₃ —SCH₃ H—SCH₂CH₂CH₃ —SCH₃ H —SOCH₂CH₂CH₃ —SCH₃ H —SO₂CH₂CH₂CH₃ —SCH₃ H—SCH(CH₃)₂ —SCH₃ H —SOCH(CH₃)₂ —SCH₃ H —SO₂CH(CH₃)₂ —SCH₃ H—SCH₂COOCH₂CH₃ —SCH₃ H —SOCH₂COOCH₂CH₃ —SCH₃ H —SO₂CH₂COOCH₂CH₃ —SCH₃ H—OCH₂CH₂SCH₃ —SCH₂CH₂OCH₃ H —OCH₂CH₂SOCH₃ —SCH₂CH₂OCH₃ H —OCH₂CH₂SO₂CH₃—SCH₂CH₂OCH₃ H —SCH₂CH₂OCH₃ —SCH₂CH₂OCH₃ H —SOCH₂CH₂OCH₃ —SCH₂CH₂OCH₃ H—SO₂CH₂CH₂OCH₃ —SCH₂CH₂OCH₃ H —SCH₂CH₂OH —SCH₂CH₂OCH₃ H —SCH₃—SCH₂CH₂OCH₃ H —SOCH₃ —SCH₂CH₂OCH₃ H —SO₂CH₃ —SCH₂CH₂OCH₃ H —SCH₂CH₃—SCH₂CH₂OCH₃ H —SOCH₂CH₃ —SCH₂CH₂OCH₃ H —SO₂CH₂CH₃ —SCH₂CH₂OCH₃ H—SCH₂CH₂CH₃ —SCH₂CH₂OCH₃ H —SOCH₂CH₂CH₃ —SCH₂CH₂OCH₃ H —SO₂CH₂CH₂CH₃—SCH₂CH₂OCH₃ H —SCH(CH₃)₂ —SCH₂CH₂OCH₃ H —SOCH(CH₃)₂ —SCH₂CH₂OCH₃ H—SO₂CH(CH₃)₂ —SCH₂CH₂OCH₃ H —SCH₂COOCH₂CH₃ —SCH₂CH₂OCH₃ H—SOCH₂COOCH₂CH₃ —SCH₂CH₂OCH₃ H —SO₂CH₂COOCH₂CH₃ —SCH₂CH₂OCH₃ H —OCH₃—OCH₂CH₂SCH₃ H —OCH₃ —OCH₂CH₂SOCH₃ H —OCH₃ —OCH₂CH₂SO₂CH₃ H —OCH₃—SCH₂CH₂OCH₃ H —OCH₃ —SOCH₂CH₂OCH₃ H —OCH₃ —SO₂CH₂CH₂OCH₃ H —OCH₃—SCH₂CH₂OH H —OCH₃ —SCH₃ H —OCH₃ —SOCH₃ H —OCH₃ —SO₂CH₃ H —OCH₃ —SCH₂CH₃H —OCH₃ —SOCH₂CH₃ H —OCH₃ —SO₂CH₂CH₃ H —OCH₃ —SCH₂CH₂CH₃ H —OCH₃—SOCH₂CH₂CH₃ H —OCH₃ —SO₂CH₂CH₂CH₂ H —OCH₃ —SCH(CH₃)₂ H —OCH₃—SOCH(CH₃)₂ H —OCH₃ —SO₂CH(CH₃)₂ H —OCH₃ —SCH₂COOCH₂CH₃ H —OCH₃—SOCH₂COOCH₂CH₃ H —OCH₃ —SO₂CH₂COOCH₂CH₃ H —OCH₂CH₂OCH₃ —OCH₂CH₂SCH₃ H—OCH₂CH₂OCH₃ —OCH₂CH₂SOCH₃ H —OCH₂CH₂OCH₃ —OCH₂CH₂SO₂CH₃ H —OCH₂CH₂OCH₃—SCH₂CH₂OCH₃ H —OCH₂CH₂OCH₃ —SOCH₂CH₂OCH₃ H —OCH₂CH₂OCH₃ —SO₂CH₂CH₂OCH₃H —OCH₂CH₂OCH₃ —SCH₂CH₂OH H —OCH₂CH₂OCH₃ —SCH₃ H —OCH₂CH₂OCH₃ —SOCH₃ H—OCH₂CH₂OCH₃ —SO₂CH₃ H —OCH₂CH₂OCH₃ —SCH₂CH₃ H —OCH₂CH₂OCH₃ —SOCH₂CH₃ H—OCH₂CH₂OCH₃ —SO₂CH₂CH₃ H —OCH₂CH₂OCH₃ —SCH₂CH₂CH₃ H —OCH₂CH₂OCH₃—SOCH₂CH₂CH₃ H —OCH₂CH₂OCH₃ —SO₂CH₂CH₂CH₃ H —OCH₂CH₂OCH₃ —SCH(CH₃)₂ H—OCH₂CH₂OCH₃ —SOCH(CH₃)₂ H —OCH₂CH₂OCH₃ —SO₂CH(CH₃)₂ H —OCH₂CH₂OCH₃—SCH₂COOCH₂CH₃ H —OCH₂CH₂OCH₃ —SOCH₂COOCH₂CH₃ H —OCH₂CH₂OCH₃—SO₂CH₂COOCH₂CH₃ —OCH₃ H —OCH₂CH₂SCH₃ —OCH₃ H —OCH₂CH₂SOCH₃ —OCH₃ H—OCH₂CH₂SO₂CH₃ —OCH₃ H —SCH₂CH₂OCH₃ —OCH₃ H —SOCH₂CH₂OCH₃ —OCH₃ H—SO₂CH₂CH₂OCH₃ —OCH₃ H —SCH₂CH₂OH —OCH₃ H —SCH₃ —OCH₃ H —SOCH₃ —OCH₃ H—SO₂CH₃ —OCH₃ H —SCH₂CH₃ —OCH₃ H —SOCH₂CH₃ —OCH₃ H —SO₂CH₂CH₃ —OCH₃ H—SCH₂CH₂CH₃ —OCH₃ H —SOCH₂CH₂CH₃ —OCH₃ H —SO₂CH₂CH₂CH₃ —OCH₃ H—SCH(CH₃)₂ —OCH₃ H —SOCH(CH₃)₂ —OCH₃ H —SO₂CH(CH₃)₂ —OCH₃ H—SCH₂COOCH₂CH₃ —OCH₃ H —SOCH₂COOCH₂CH₃ —OCH₃ H —SO₂CH₂COOCH₂CH₃—OCH₂CH₂OCH₃ H —OCH₂CH₂SCH₃ —OCH₂CH₂OCH₃ H —OCH₂CH₂SOCH₃ —OCH₂CH₂OCH₃ H—OCH₂CH₂SO₂CH₂ —OCH₂CH₂OCH₃ H —SCH₂CH₂OCH₃ —OCH₂CH₂OCH₃ H —SOCH₂CH₂OCH₃—OCH₂CH₂OCH₃ H —SO₂CH₂CH₂OCH₃ —OCH₂CH₂OCH₃ H —SCH₂CH₂OH —OCH₂CH₂OCH₃ H—SCH₃ —OCH₂CH₂OCH₃ H —SOCH₃ —OCH₂CH₂OCH₃ H —SO₂CH₃ —OCH₂CH₂OCH₃ H—SCH₂CH₃ —OCH₂CH₂OCH₃ H —SOCH₂CH₃ —OCH₂CH₂OCH₃ H —SO₂CH₂CH₃ —OCH₂CH₂OCH₃H —SCH₂CH₂CH₃ —OCH₂CH₂OCH₃ H —SOCH₂CH₂CH₃ —OCH₂CH₂OCH₃ H —SO₂CH₂CH₂CH₃—OCH₂CH₂OCH₃ H —SCH(CH₃)₂ —OCH₂CH₂OCH₃ H —SOCH(CH₃)₂ —OCH₂CH₂OCH₃ H—SO₂CH(CH₃)₂ —OCH₂CH₂OCH₃ H —SCH₂COOCH₂CH₃ —OCH₂CH₂OCH₃ H—SOCH₂COOCH₂CH₃ —OCH₂CH₂OCH₃ H —SO₂CH₂COOCH₂CH₃

The compounds according to the invention are prepared, for example,starting from the compounds of the formula I known from WO98/42707 inwhich at least one of the substituents R4a, R4b, R5a and R5b is hydroxyl(referred to as “starting materials” hereinbelow). Starting with thestarting materials, the compounds according to the invention can beprepared by various routes, depending on which end product is desired,for example as outlined below:

a) by acid-catalyzed etherification of the starting materials withcompounds of the formula R4′-H or R5′-H.

b) by reacting the starting materials (if appropriate after they havebeen sulfidized) with compounds of the formulaR9-S(O)_(n)—(CH₂)_(m)-Hal, HO—(CH₂)_(m)-Hal, R9-O—(CH₂)_(m)-Hal,R9-S(O)_(p)—(CH₂)_(m)-Hal, R9-Hal, R9-S(O)_(n)-alk1-Hal, HO-alk1-Hal,R9-O-alk1-Hal or R9S(O)_(p)-alk1-Hal or R10-S(O)_(r)—(CH₂)_(q)-Hal,HO—(CH₂)_(q)-Hal, R10-O—(CH₂)_(q)-Hal, R10-S(O)_(t)—(CH₂)_(q)-Hal,R10-Hal, R10-S(O)_(r)-alk2-Hal, HO-alk2-Hal, R10-O-alk2-Hal orR10-S(O)_(t)-alk2-Hal, where Hal is a halogen atom, preferably achlorine, bromine or iodine atom, preferably in the presence of anauxillary base or after prior deprotonation of the starting material.

Depending on the nature of the radical R4′ or R5′, it may beadvantageous not to introduce the entire radical R4′ or R5′ into thestarting materials by the appropriate reaction. Rather, it is alsofeasible to employ a two- or multi-step procedure, as described in anexemplary manner in the European Patent Application 235 575, forexample.

For the compounds of the formula I according to the invention in whichn, p, r and/or t are different from the number 0, the reaction accordingto a) or b) is, if appropriate, followed by oxidation.

The oxidation of the sulfides to the sulfoxides or sulfones is carriedout under the conditions known to the person skilled in the art foroxidizing sulfides to sulfoxides and sulfones respectively, [see, forexample, J. Drabowicz and M. Mikolajczyk, Organic preparations andprocedures int. 14(1-2), 45-89 (1982) or E. Block in S. Patai, TheChemistry of Functional Groups, Supplement E. Part 1, pp. 539-608, JohnWiley and Sons (Interscience Publication), 1980]. Suitable oxidizingagents are all reagents which are customarily used for oxidizingsulfides to sulfoxides or sulfones.

Sulfoxides are optically active compounds, so that for n, p, r and/ort=1, one or more further chiral centers are introduced into themolecule. With respect to the sulfoxides, the invention therefore alsoembraces both the enantiomers and diastereomers and their mixtures andracemates. The enantiomers can be separated in a manner known per se(for example by preparing and separating corresponding diastereoisomericcompounds).

The compounds of the formulae R4′-H, R5′-H, R9-S(O)_(n)—(CH2)_(m)-Hal,HO—(CH2)_(m)-Hal, R9-O—(CH₂)_(m)-Hal, R9-S(O)_(p)—(CH₂)_(m)-Hal, R9-Hal,R9-S(O)_(n)-alk1-Hal, HO-alk1-Hal, R9-O-alk1-Hal, R9-S(O)_(p)-alk1-Hal,R10-S(O)_(r)—(CH₂)_(q)-Hal, HO—(CH₂)_(q)-Hal, R10-O—(CH₂)_(q)-Hal,R10-S(O)_(t)—(CH₂)_(q)-Hal, R10-Hal, R10-S(O)_(r)-alk2-Hal, HO-alk2-Hal,R10-O-alk2-Hal, R10-S(O)_(t)-alk2-Hal and the compounds required fortheir preparation are known, or they can be prepared in a manner knownper se.

The following examples illustrate the invention in more detail, withoutlimiting it. The compounds according to the invention can be prepared ina manner analogous to that described in the examples. The abbreviationRT stands for room temperature, h stands for hour(s), m.p. stands formelting point and decomp. stands for decomposition.

EXAMPLES 1.(7R,8R,9R)-2,3-dimethyl-8-hydroxy-7-(2-methylthioethyloxy)-9-phenyl-7,8,9,10-tetrahydroimidazo[1,2-h][1,7]naphthyridine

1 g of(7R,8R,9R)-7,8-dihydroxy-2,3-dimethyl-9-phenyl-7,8,9,10-tetrahydroimidazo[1,2-h][1,7]naphthyridine,dissolved in 30 ml of dioxane and 5 ml of dimethyl-formamide, is admixedwith 0.63 g of concentrated sulfuric acid and 1 g of2-methylmercaptoethanol. The mixture is stirred at RT for 3 h, pouredinto ice-water (200 ml), adjusted to pH 8 using 2 N aqueous sodiumhydroxide solution and extracted three times with methylene chloride.The solvent is stripped off under reduced pressure and the oily residuethat remains is purified on silica gel (mobile phase: diethyl ether).This gives 80 mg of the title compound of m.p. 118-9° C. (diisopropylether).

2.(7S,8R,9R)-2,3-dimethyl-8-hydroxy-7-(2-methylthioethyloxy)9-phenyl-7,8,9,10-tetrahydroimidazo[1,2-h][1,7]naphthyridine

The mother liquor from Example 1 gives, after purification on silica gel(mobile phase: diethyl ether), 40 mg of the title compound of m.p.109-10° C.

3.(7R,8R,9R)-2,3-dimethyl-8-hydroxy-7-(2-methylsulphinylethoxy)-9phenyl-7,8,9,10-tetrahydroimidazo[1,2-h][1,7]naphthyridine

130 mg of sodium metaperiodate, dissolved in 1 ml of water, is added toa solution of 200 mg of(7R,8R,9R)-2,3-dimethyl-8-hydroxy-7-(2-methylthioethoxy)-9-phenyl-7,8,9,10-tetrahydroimidazo[1,2-h]-[1,7]naphthyridinein 5 ml of methanol. After two hours stirring at room temperature, 50 mlof water are added. The mixture is extracted three times withdichloromethane, the organic phases are collectively washed with waterand dried over sodium sulphate. The solvent is removed in vacuo and theremaining residue is purified by chromatography on silica gel (eluent:ethylacetate/methanol=10/1). 100 mg of the title compound of m.p.105-106° C. are obtained.

4.(7S,8R,9R)-2,3-dimethyl-8-hydroxy-7-(2-methylsulphinylethoxy)-9-phenyl-7,8,9,10-tetrahydroimidazo[1,2-h][1,7]naphthyridine

80 mg of the title compound of m.p. 85-87° C. are obtained by oxidationof 200 mg of(7S,8R,9R)-2,3-dimethyl-8-hydroxy-7-(2-methylthioethoxy)-9-phenyl-7,8,9,10-tetrahydro-imidazo[1,2-h][1,7]naphthyridineanalogously to Example 3.

5.(7R,8R,9R)-2,3dimethyl-8-hydroxy-7-(ethylthio)-9-phenyl-7,8,9,10-tetrahydro-imidazo[1,2-h][1,7]naphthyridine

1.9 g of concentrated sulphuric acid are added slowly at roomtemperature with stirring to 3 g of(7R,8R,9R)-7,8-dihydroxy-2,3-dimethyl-9-phenyl-7,8,9,10-tetra-hydroimidazo[1,2-h][1,7]naphthyridine,dissolved in a mixture of 40 ml of dry dioxan and 4 ml of ethylsulfide:The temperature is brought to 50° C. by external heating and is thenkept for 15 min. After cooling to room temperature, the mixture ispoured into 300 g of a mixture of crushed ice and water. The pH isadjusted to neutral by adding aqueous 2N sodium hydroxide solution. Themixture is extracted three times (50 ml each) with ethyl acetate, theorganic layers are collectively washed with water and dried overpotassium carbonate. The solvent is stripped off under reduced pressureand the solid residue that remains is purified by chromatography onsilica gel (mobile phase: diethyl ether). 700 mg of the title compoundof m.p. 220-223° C. are obtained after crystallisation from 2-propanol.

6.(7S,8R,9R)-2,3-dimethyl-8-hydroxy-7-(ethylthio)-9-phenyl-7,8,9,10-tetrahydro-imidazo[1,2-h][1,7]naphthyridine

400 mg of the title-compound of m.p. 235-236° C. are obtained aftercrystallisation from isopropyl acetate by chromatographic purificationon silica gel of the solid residue of Example 5.

COMMERCIAL UTILITY

The compounds of the formula I and their salts have valuablepharmacological properties which make them commercially utilizable. Inparticular, they exhibit marked inhibition of gastric acid secretion andan excellent gastric and intestinal protective action in warm-bloodedanimals, in particular humans. In this connection, the compoundsaccording to the invention are distinguished by a high selectivity ofaction, an advantageous duration of action, a particularly good enteralactivity, the absence of significant side effects and a largetherapeutic range.

“Gastric and intestinal protection” in this connection is understood asmeaning the prevention and treatment of gastrointestinal diseases, inparticular of gastrointestinal inflammatory diseases and lesions (suchas, for example, gastric ulcer, duodenal ulcer, gastritis, hyperacidicor medicament-related functional dyspepsia), which can be caused, forexample, by microorganisms (e.g. Helicobacter pylori), bacterial toxins,medicaments (e.g. certain antiinflammatories and antirheumatics),chemicals (e.g. ethanol), gastric acid or stress situations.

In their excellent properties, the compounds according to the inventionsurprisingly prove to be clearly superior to the compounds known fromthe prior art in various models in which the antiulcerogenic and theantisecretory properties are determined. On account of these properties,the compounds of the formula I and their pharmacologically acceptablesalts are outstandingly suitable for use in human and veterinarymedicine, where they are used, in particular, for the treatment and/orprophylaxis of disorders of the stomach and/or intestine. A furthersubject of the invention are therefore the compounds according to theinvention for use in the treatment and/or prophylaxis of theabovementioned diseases.

The invention likewise includes the use of the compounds according tothe invention for the production of medicaments which are employed forthe treatment and/or prophylaxis of the abovementioned diseases.

The invention furthermore includes the use of the compounds according tothe invention for the treatment and/or prophylaxis of the abovementioneddiseases.

A further subject of the invention are medicaments which comprise one ormore compounds of the formula I and/or their pharmacologicallyacceptable salts.

The medicaments are prepared by processes which are known per se andfamiliar to the person skilled in the art. As medicaments, thepharmacologically active compounds according to the invention (=activecompounds) are either employed as such, or preferably in combinationwith suitable pharmaceutical auxiliaries or excipients in the form oftablets, coated tablets, capsules, suppositories, patches (e.g. as TTS),emulsions, suspensions or solutions, the active compound contentadvantageously being between 0.1 and 95% and it being possible to obtaina pharmaceutical administration form exactly adapted to the activecompound and/or to the desired onset of action (e.g. a sustained-releaseform or an enteric form) by means of the appropriate selection of theauxiliaries and excipients.

The auxiliaries and excipients which are suitable for the desiredpharmaceutical formulations are known to the person skilled in the arton the basis of his/her expert knowledge. In addition to solvents,gel-forming agents, suppository bases, tablet auxiliaries and otheractive compound excipients, it is possible to use, for example,antioxidants, dispersants, emulsifiers, antifoams, flavor corrigents,preservatives, solubilizers, colorants or, in particular, permeationpromoters and complexing agents (e.g. cyclodextrins).

The active compounds can be administered orally, parenterally orpercutaneously.

In general, it has proven advantageous in human medicine to administerthe active compound(s) in the case of oral administration in a dailydose of approximately 0.01 to approximately 20, preferably 0.05 to 5, inparticular 0.1 to 1.5, mg/kg of body weight, if appropriate in the formof several, preferably 1 to 4, individual doses to achieve the desiredresult. In the case of a parenteral treatment, similar or (in particularin the case of the intravenous administration of the active compounds),as a rule, lower doses can be used. The establishment of the optimaldose and manner of administration of the active compounds necessary ineach case can easily be carried out by any person skilled in the art onthe basis of his/her expert knowledge.

If the compounds and/or their salts according to the invention are to beused for the treatment of the abovementioned diseases, thepharmaceutical preparations can also contain one or morepharmacologically active constituents of other groups of medicaments,for example: tranquilizers, (for example from the group of thebenzodiazepines, for example diazepam), spasmolytics (for example,bietamiverine or camylofin), anticholinergics, (for example,oxyphencyclimine or phencarbamide), local anesthetics, (for example,tetracaine or procaine), and, if appropriate, also enzymes, vitamins oramino acids.

To be emphasized in this connection is in particular the combination ofthe compounds according to the invention with pharmaceuticals whichinhibit acid secretion, such as, for example, H₂ blockers (e.g.cimetidine, ranitidine), H⁺/K⁺ ATPase inhibitors (e.g. omeprazole,pantoprazole), or further with so-called peripheral anticholinergics(e.g. pirenzepine, telenzepine) and with gastrin antagonists with theaim of increasing the principal action in an additive or super-additivesense and/or of eliminating or of decreasing the side effects, orfurther the combination with antibacterially active substances (such as,for example, cephalosporins, tetracyclines, penicillins, macrolides,nitroimidazoles or alternatively bismuth salts) for the control ofHelicobacter pylon. Suitable antibacterial co-components which may bementioned are, for example, meziocillin, ampicillin, amoxicillin,cefalothin, cefoxitin, cefotaxim, imipenem, gentamycin, amikacin,erythromycin, ciprofloxacin, metronidazole, clarithromycin, azithromycinand combinations thereof (for example clarithromycin+metronidazole).

PHARMACOLOGY

The excellent gastric protective action and the gastric acidsecretion-inhibiting action of the compounds according to the inventioncan be demonstrated in investigations on animal experimental models. Thecompounds according to the invention investigated in the model mentionedbelow have been provided with numbers which correspond to the numbers ofthese compounds in the examples.

Testing of the Secretion-inhibiting Action on the Perfused Rat Stomach

In Table A which follows, the influence of the compounds according tothe invention on the pentagastrin-stimulated acid secretion of theperfused rat stomach after intravenous administration in vivo is shown.

TABLE A Dose (μmol/kg) Inhibition of acid secretion No. i.v. (%) 1 3 1005 3 100

Methodology

The abdomen of anesthetized rats (CD rat, female, 200-250 g; 1.5 g/kgi.m. urethane) was opened after tracheotomy by a median upper abdominalincision and a PVC catheter was fixed transorally in the esophagus andanother via the pylorus such that the ends of the tube just projectedinto the gastric lumen. The catheter leading from the pylorus ledoutwards into the right abdominal wall through a side opening.

After thorough rinsing (about 50-100 ml), warm (37° C.) physiologicalNaCl solution was continuously passed through the stomach (0.5 ml/min,pH 6.8-6.9; Braun-Unita 1). The pH (pH meter 632, glass electrode EA147; φ=5 mm, Metrohm) and, by titration with a freshly prepared 0.01 NNaOH solution to pH 7 (Dosimat 665 Metrohm), the secreted HCl weredetermined in the effluent in each case collected at an interval of 15minutes.

The gastric secretion was stimulated by continuous infusion of 1 μg/kg(=1.65 ml/h) of i.v. pentagastrin (left femoral vein) about 30 min afterthe end of the operation (i.e. after determination of 2 preliminaryfractions). The substances to be tested were administered intravenouslyin a 1 ml/kg liquid volume 60 min after the start of the continuouspentagastrin infusion.

The body temperature of the animals was kept at a constant 37.8-38° C.by infrared irradiation and heat pads (automatic, stepless control bymeans of a rectal temperature sensor).

What is claimed is:
 1. A compound of the formula I

in which R1 is 1-4C-alkyl, R2 is 1-4C-alkyl or hydroxy-1-4C-alkyl, R3 ishydrogen or halogen, one of the substituents R4a and R4b is hydrogen andthe other is hydrogen, hydroxyl, 1-4C-alkoxy, 1-4C-alkoxy-1-4C-alkoxy,1-4C-alkylcarbonyloxy or the radical R4′, or R4a and R4b together are O(oxygen), where, R4′ is —O—(CH₂)_(m)S(O)_(n)—R9, —S(O)_(n)—(CH₂)_(m)—OH,—S(O)_(n)—(CH₂)_(m)—O—R9, —S(O)_(n)—(CH₂)_(m)—S(O)_(p)—R9,—O-alk1-S(O)_(n)—R9, —S(O)_(n)—R9, —S(O)_(n)-alk1-OH,—S(O)_(n)-alk1-O-R9 or —S(O)_(n)-alk1-S(O)_(p)-R9, in which R9 is1-7C-alkyl, halo-1-4C-alkyl, hydroxy-1-4C-alkyl, 1-4C-alkoxy-1-4C-alkyl,carboxy-1-4C-alkyl, 1-4C-alkoxycarbonyl-1-4C-alkyl ordi-1-4C-alkylamino-1-4C-alkyl, Ar or Ar-1-4C-alkyl, where Ar is phenylor substituted phenyl having one, two or three identical or differentsubstituents selected from the group consisting of 1-4C-alkyl,1-4C-alkoxy, 1-4C-alkylcarbonyl, 1-4C-alkoxycarbonyl, halogen,trifluoromethyl, difluoromethoxy, trifluoromethoxy, amino,1-4C-alkoxycarbonylamino, 1-4C-alkoxy-1-4C-alkoxycarbonylamino andnitro, alk1 is 1-4C-alkyl-, hydroxyl-, oxo-, carboxyl-, halogen-,amino-, 1-4C-alkoxycarbonylamino- or phenyl-substituted 2-7C-alkylene or3-4C-alkenylene, m is an integer from 2 to 7, n is the number 0, 1 or 2and p is the number 0, 1 or 2, one of the substituents R5a and R5b ishydrogen and the other is hydrogen, hydroxyl, 1-4C-alkoxy,1-4C-alkoxy-1-4C-alkoxy, 1-4C-alkylcarbonyloxy or the radical R5′, orR5a and R5b together are O (oxygen) where R5′ is—O—(CH₂)_(q)—S(O)_(r)—R10, —S(O)_(r)—(CH₂)_(q)—OH,—S(O)_(r)—(CH₂)_(q)—O—R10, —S(O)_(r)(CH₂)_(q)—S(O)_(t)—R10,—O-alk2-S(O)_(r)—R10, —S(O)_(r)—R10, —S(O)_(r)-alk2-OH,—S(O)_(r)alk2-O—R10 or —S(O)_(r)-alk2-S(O)_(t)—R10, in which R10 is1-7C-alkyl, halo-1-4C-alkyl, hydroxy-1-4C-alkyl, 1-4C-alkoxy-1-4C-alkyl,carboxy-1-4C-alkyl, 1-4C-alkoxycarbonyl-1-4C-alkyl ordi-1-4C-alkylamino-1-4C-alkyl, Ar or Ar-1-4C-alkyl, where Ar is phenylor substituted phenyl having one, two or three identical or differentsubstituents selected from the group consisting of 1-4C-alkyl,1-4C-alkoxy, 1-4C-alkylcarbonyl, 1-4C-alkoxycarbonyl, halogen,trifluoromethyl, difluoromethoxy, trifluoromethoxy, amino,1-4C-alkoxycarbonylamino, 1-4C-alkoxy-1-4C-alkoxycarbonylamino andnitro, alk2 is 1-4C-alky-, hydroxyl-, oxo-, carboxyl-, halogen-, amino-,1-4C-alkoxycarbonylamino- or phenyl-substituted 2-7C-alkylene or3-4C-alkenylene, q is an integer from 2 to 7, r is the number 0, 1 or 2and t is the number 0, 1 or 2, R6 is hydrogen, halogen, 1-4C-alkyl,1-4C-alkoxy, 1-4C-alkoxycarbonylamino,1-4C-alkoxy-1-4C-alkoxycarbonylamino or trifluoromethyl, R7 is hydrogen,halogen, 1-4C-alkyl or 1-4C-alkoxy and R8 is hydrogen or 1-4C-alkyl, andits salts, where one of the substituents R4a and R4b has to be R4′and/or one of the substituents R5a and R5b has to be R5′.
 2. A compoundas claimed in claim 1, of the formula I*

in which R1 is 1-4C-alkyl, R2 is 1-4C-alkyl or hydroxy-1-4C-alkyl, R3 ishydrogen, one of the substituents R4a and R4b is hydrogen and the otheris hydrogen, hydroxyl, 1-4C-alkoxy, 1-4C-alkoxy-1-4C-alkoxy or theradical R4′, where R4′ is —O—(CH₂)_(m)—S(O)_(n)—R9,—S(O)_(n)—(CH₂)_(m)—OH, —S(O)_(n)—(CH₂)_(m)—O—R9,—S(O)_(n)—(CH₂)_(m)—S(O)_(p)—R9 or —S(O)_(n)—R9, in which R9 is1-7C-alkyl, halo-1-4 C-alkyl, hydroxy-1-4C-alkyl or1-4C-alkoxy-1-4C-alkyl, m is an integer from 2 to 7, n is the number 0,1 or 2 and p is the number 0, 1 or 2, one of the substituents R5a andR5b is hydrogen and the other is hydrogen, hydroxyl, 1-4C-alkoxy,1-4C-alkoxy-1-4C-alkoxy or the radical R5′, where R5′ is—O—(CH₂)_(q)—S(O)_(r)—R10, —S(O)_(r)—(CH₂)_(q)—OH,—S(O)_(r)(CH₂)_(q)—O—R10, —S(O)_(r)—(CH₂)_(q)—S(O)_(t)—R10 or—S(O)_(r)—R10, in which R10 is 1-7C-alkyl, halo-1-4C-alkyl,hydroxy-1-4C-alkyl or 1-4C-alkoxy-1-4C-alkyl, q is an integer from 2 to7, r is the number 0, 1 or 2 and t is the number 0, 1 or 2, R6 ishydrogen, halogen or trifluoromethyl, R7 is hydrogen or halogen and R8is hydrogen, and its salts, where one of the substituents R4a and R4bhas to be R4′ and/or one of the substituents R5a and R5b has to be R5′.3. A compound I* as claimed in claim 2 in which R1 is 1-4C-alkyl, R2 is1-4C-alkyl, R3 is hydrogen, one of the substituents R4a and R4b ishydrogen and the other is R4′ where R4′ is —O—(CH₂)_(m)—S(O)_(n)—R9,—S(O)_(n)—R9, —S(O)_(n)—(CH₂)_(m)—OH or —S(O)_(n)—(CH₂)_(m)—O—R9, inwhich R9 is 1-4C-alkyl, m is the number 2 or 3 and n is the number 0, 1or 2, one of the substituents R5a and R5b is hydrogen and the other ishydroxyl, R6 is hydrogen, R7 is hydrogen and R8 is hydrogen, and itssalts.
 4. A compound I* as claimed in claim 2 in which R1 is 1-4C-alkyl,R2 is 1-4C-alkyl, R3 is hydrogen, one of the substituents R4a and R4b ishydrogen and the other is R4′, where R4′ is —O—(CH₂)_(m)—S(O)_(n)—R9,—S(O)_(n)—R9, —S(O)_(n)—(CH₂)_(m)—OH or —S(O)_(n)—(CH₂)_(m)—O—R9, inwhich R9 is 1-4C-alkyl, m is the number 2 or 3 and n is the number 0, 1or 2, one of the substituents R5a and R5b is hydrogen and the other is1-4C-alkoxy or 1-4C-alkoxy-1-4C-alkoxy, R6 is hydrogen, R7 is hydrogenand R8 is hydrogen, and its salts.
 5. A compound I* as claimed in claim2 in which R1 is 1-4C-alkyl, R2 is 1-4C-alkyl, R3 is hydrogen, one ofthe substituents R4a and R4b is hydrogen and the other is R4′, where R4′is —O—(CH₂)_(m)—S(O)_(n)—R9, —S(O)_(n)—R9, —S(O)_(n)—(CH₂)_(m)—OH or—S(O)_(n)—(CH₂)_(m)—O—R9, in which R9 is 1-4C-alkyl, m is the number 2or 3 and n is the number 0, 1 or 2, one of the substituents R5a and R5bis hydrogen and the other is R5′, where R5′ is —O—(CH₂)_(q)—S(O)_(r)R10,—S(O)_(r)—R10, —S(O)_(r)—(CH₂)_(q)—OH or —S(O)_(r)—(CH₂)_(q)—O—R10, inwhich R10 is 1-4C-alkyl, q is the number 2 or 3 and r is the number 0, 1or 2, R6 is hydrogen, R7 is hydrogen and R8 is hydrogen, and its salts.6. A compound I* as claimed in claim 2 in which R1 is 1-4C-alkyl, R2 is1-4C-alkyl, R3 is hydrogen, one of the substituents R4a and R4b ishydrogen and the other is 1-4C-alkoxy or 1-4C-alkoxy-1-4C-alkoxy, one ofthe substituents R5a and R5b is hydrogen and the other is R5′, where R5′is —O—(CH₂)_(q)—S(O)_(r)—R10, —S(O)_(r)—R10, —S(O)_(r)—(CH₂)_(q)—OH or—S(O)_(r)—(CH₂)_(q)—O—R10, in which R10 is 1-4C-alkyl, q is the number 2or 3 and r is the number 0, 1 or 2, R6 is hydrogen, R7 is hydrogen andR8 is hydrogen, and its salts.
 7. A compound I* as claimed in claim 2,in which R5b is hydrogen.
 8. A compound I* as claimed in claim 2 inwhich R5b is hydrogen and R4a is hydrogen.
 9. A pharmaceuticalcomposition comprising a compound as claimed in claim 1 and/or apharmacologically acceptable salt thereof together with a customarypharmaceutical auxiliary and/or excipient.
 10. A method of preparing apharmaceutical composition which comprises combining a pharmaceuticalauxiliary and/or excipient with a pharmacologically active compound forthe prevention or treatment of a gastrointestinal disorder, or apharmacologically acceptable salt thereof, wherein the pharmacologicallyactive compound is a compound as claimed in claim
 1. 11. A method ofpreventing or treating an amenable gastrointestinal disorder, whichcomprises administering an effective amount of a compound of claim 1 ora pharmacologically acceptable salt thereof to a subject in need of suchtherapy.